Temporal coordination has been proposed as a fundamental underlying mechanism of attention in the mammalian brain and disturbances in temporal coordination are found in many brain disorders, including autism and schizophrenia, where they are potentially central to the defects. We have developed models for sleep and attention in the fruit fly Drosophila, and found that arousal levels in the fly brain are associated with different levels of temporal coordination (coherence). This proposal tests the idea that arousal states in the Drosophila brain, from sleep to attention, are brain-wide processes mediated by the degree and combinations of physiological coupling or linkage. This is measurable electrophysiologically as the level of temporal coordination (coherence) between various regions of the brain, being lowest in sleep and highest in attention-like states. Furthermore, we use genetic variants to test the idea that two highly conserved systems that control and modulate arousal at the molecular level in mammals and flies (dopamine and the EGFR signal transduction pathway) do so by their action on coherence. Finally, we test whether direct, local perturbations of coherence with hypo- or hyper-exciting transgenes alter arousal states. Thus, the goal is to integrate the molecular, physiological, and behavioral levels in an effort to understand the role and regulation of temporal coordination in producing different brain states. Specific Aims 1. Temporal coordination across the brain from sleep to attention: How much of the brain participates? Which regions? Are they the same for sleep and attention? 2. What effect do the known arousal systems in Drosophila have on attention and on temporal coordination? 3. How do genetic perturbations of temporal coordination, asymmetrically and by manipulation of commissures, alter arousal states? PUBLIC HEALTH RELEVANCE: Disturbances of timing in the brain are a shared and potentially critical feature of many brain disorders, including autism and schizophrenia. Our ability to address the impairments associated with these disorders would therefore benefit from a better understanding of the role of timing between different parts of the brain and the mechanisms that regulate it.